Yulin Ge1, Zhongwei Zhang1,
Hanzhang Lu2, Lin Tang1, Hina
Jaggi1, James Babb1, Joseph
Herbert3, and Robert I Grossman11Department of Radiology, New York University
Langone Medical Center, New York City, NY, United
States,2Advanced
Imaging Research Center, University of Texas
Southwestern Medical Center,3Department
of Neurology, New York University Langone Medical
Center, New York City, NY, United States

Using a newly developed T2-relaxation-under-spin-tagging
(TRUST) MRI, a novel noninvasive technique for measuring
brain venous sinus blood oxygenation (Yv), we have
investigated the global oxygen metabolism changes in
patients with relapsing remitting multiple sclerosis
(MS). We found significantly increased Yv in patients
(mean/SD: 64.2/5.1%) as compared to control subjects
(mean/SD: 59.6/4.8%), and Yv has significant correlation
with the total lesion load (r=0.44, P=0.03), but not
with brain atrophy. Our findings suggest that
significant underutilization of oxygen in MS might
reflect the diffuse neuronal cells inactive state due to
chronic and diffuse nature of the disease rather than
parenchyma tissue loss.

Wei Bian1,2, Kristin Harter3,
Kathryn Hammond Rosenbluth4, Duan Xu2,
Douglas AC Kelley2, Daniel Vigneron2,
Sarah J Nelson2,5, and Daniel Pelletier61Joint Graduate Program in BioEngineering at
UCSF & UCB, University of California San Francisco, San
Francisco, CA, United States,2Department
of Radiology and Biomedical Imaging, University of
California San Francisco, San Francisco, CA, United
States,3School
of Pharmacy, University of California San Francisco, San
Francisco, CA, United States,4Department
of Neurological Surgery, University of California San
Francisco, San Francisco, CA, United States,5Department
of BioEngineeing and Therapeutic Sciences, Unviersity of
California San Francisco, San Francisco, CA, United
States,6Department
of Neurology, University of California San Francisco,
San Francisco, CA, United States

MRI at 7 Tesla can produce high-resolution phase images
of MS lesions that quantify the local field shifts
sensitive to iron. A subset of MS lesions visible with
phase imaging shows a distinct peripheral ring. The
purpose of this serial in vivo 7T study was to follow
the evolution of MS lesions showing a phase contrast
ring for up to 2.5 years. Our results support the
concept that once they have been formed, the peripheral
rings in MS white lesions remain stable with time. The
biological source of this phase contrast signal remains
to be elucidated.

13:50

603.

Quantitative
characterization of cortical pathology in multiple sclerosis
using surface-based analysis of T2* relaxation at 7T

The ability to detect and to classify in vivo gray
matter (GM) lesions in multiple sclerosis (MS) is
required to better understand pathological processes
associated with disease progression and disability. We
combined ultra high field MRI (7T) with surface-based
analysis to achieve quantitative assessment of cortical
changes in MS. Results show a significant T2* increase
in MS patients versus controls. This increase may
reflect disseminated cortical pathology described in
post-mortem examination. Surface-based analysis combined
with quantitative measures has the potential to improve
our understanding of the disease phenotypes via the
discovery of specific quantitative biomarkers of
cortical pathology in MS.

Lazar Fleysher1, Niels Oesingmann2,
Ryan Brown1, Hina Jaggi1, Graham
Wiggins1, Daniel Sodickson1,
Joseph Herbert3, and Matilde Inglese1,41Radiology, NYU School of Medicine, New York,
New York, United States,2Siemens
Medical Solutions USA, Malvern, PA, United States,3Neurology,
NYU School of Medicine, New York, New York, United
States,4Neurology,
NYU School of Medicine, New York, New York

Intracellular Sodium Concentration (ISC) and
Intracellular Sodium Volume Fraction (ISVF) are often
used as operational measures of tissue viability.
Elevated brain tissue sodium concentration (TSC) has
been reported previously in MS patients. However, TSC is
sensitive but not specific to variations in ISC and
ISVF. In this work, we employ single- (SQ) and
triple-quantum-filtered (TQF) sodium MRI at 7T to
evaluate ISC and ISVF in MS patients. We found that ISCs
in the MS patients are higher than in healthy controls
indicating accumulation of intracellular sodium. In
addition, we observed that the patientsí ISFVs are lower
than those of healthy controls indicating loss of the
intracellular volume.

There have been a plethora of reports on the MS atrophic
brain using whole brain or regional metrics combined
with voxel-based and fiber tracking approaches. To date
there has been no comprehensive report of the
simultaneous fusion and application of standardized
brain atlas and multimodal quantitative MRI methods on
both normal-appearing white matter (NAWM) and norma-appearing
subcortical and cortical gray matter (NAGM) of the MS
brain relative to healthy controls with account of late
development, natural aging and lesion effects. We used
lesion spatial mapping methods and FreeSurfer volumetry
in combination with relaxation and diffusion tensor
imaging methods to obtain regional volumetry of both
deep and lobar NAWM and cortical and subcortical NAGM in
a cohort of relapsing and remitting (RRMS) patients and
healthy adult controls. We demonstrate the utility of
this approach by showing strong correlations of regional
metrics with the expanded disability status score (EDSS).
Our results consolidate published literature and offer a
window to model the pathogensis of MS using a brain
system level.

14:20

606.

Ten-year brain atrophy
rate and its relevance to disability in multiple sclerosis

This ongoing study is the first report of a long-term
(10 years) follow-up on brain atrophy in MS. Brain
volume loss is, on average, -5% in MS patients and -3%
in normal controls. It seems to be a global process,
involving all tissue compartments. Brain atrophy rate,
both global and in the grey matter, was associated to
clinical worsening, particularly in subject with higher
frequency of clinical relapses and progressing
disability. This suggests that long-term global and grey
matter brain atrophy change may provide a valuable
outcome of longstanding disability and progression in
patients with MS

14:30

607.

Reversible NAA decreases
in active MS lesions are not due solely to water content
changes

Irene Vavasour1, Cornelia Laule1,2,
Madeleine Hodgson3, David Li1,
Anthony Traboulsee4, Burkhard Maedler5,
and Alexander MacKay1,31Radiology, University of British Columbia,
Vancouver, British Columbia, Canada,2Pathology
and Laboratory Medicine, University of British Columbia,
Vancouver, British Columbia, Canada,3Physics
and Astronomy, University of British Columbia,
Vancouver, British Columbia, Canada,4Medicine
(Neurology), University of British Columbia, Vancouver,
British Columbia, Canada,5Neurosurgery,
University of Bonn, Germany

Previous magnetic resonance spectroscopy studies have
shown a decrease in N-acetyl-aspartate (NAA)
concentration when a new MS lesion appears followed by a
subsequent rise. The most plausible explanation is that
dilution from increased water content (WC) related to
edema causes NAA to decrease while edema resolution
leads to an NAA increase. Scanning monthly over 6
months, NAA concentrations of twelve new lesions were
extracted using LCModel and corrected for relaxation and
WC. Even after taking into account WC changes, NAA
showed a reversible decrease in new lesions. The
reversible NAA changes in new lesions are not a simple
dilution effect.

This study assessed iron accumulation in white matter
lesions of 116 MS patients using R2* relaxometry.
Intralesional R2* rates were compared to normal white
matter of age matched controls and were related to
clinical parameters. They showed a negative correlation
with T2 lesion load and a positive correlation with
brain atrophy and were significantly decreased in MS
patients compared to white matter R2* rates of controls.
The results of this work do not support expectations of
increased iron accumulation in MS lesions, but rather
indicate lower levels compared to normal white matter.

This study aims to characterize longitudinal alterations
of white matter (WM) over a period of 2 years in
different clinical forms of multiple sclerosis (MS)
using tract-based spatial statistics (TBSS). Significant
alterations of diffusivity including FA decrease, and
λ1, λ2 and λ3 increases were mostly found in the right
hemisphere of relapsing-remitting (RR) patients,
particularly in the external capsule (EC). Region of
interest (ROI) analysis of this region confirmed these
results and allowed the quantification of these changes
over time. The comparison between left and right EC of
DTI metrics variations over time showed significant
decreases of FA and increases of λ1, λ2 and λ3 in the
right ROI. This finding probably reflects an evolving
process spreading from the left to the right hemisphere
that may result from demyelination and/or remyelination
processes in the right and left hemispheres,
respectively.

Klaus Schmierer1,2, Dan Tozer2,
and Axel Petzold2,31Barts and The London School of Medicine &
Dentistry, London, England, United Kingdom,2Neuroinflammation,
UCL Institute of Neurology, London, United Kingdom,3Free
University Medical Centre, Amsterdam, Netherlands

Multiple sclerosis (MS) affects the phosphorylation and
thus the proton binding capacity of axonal neurofilament
(Nf) proteins. Macromolecules can be quantified using
magnetization transfer ratio (MTR). We explored in post
mortem brain of 12 patients with MS whether in
non-lesional white matter (NLWM) MTR is associated with
Nf phosphoforms, as a biomarker of axonal
phosphorylation in NLWM. Indeed, the concentration of
hyperphosphorylated Nf correlated with T1(r=0.7;
p= 0.01) and (inversely) with MTR (r=-0.76 p<0.01) (fig
3) suggesting that both MTR and T1may be
markers of axonal integrity in NLWM.